For several years, the focus of research in this laboratory has been the study of olfactory receptor cell differentiation with attention to the extrinsic influences that modulate differentiation, particularly those influences originating in the olfactor bulb. We have pioneered the development and utilization of in vitro techniques for these studies. We will continue this research on receptor-target interaction, and, three other goals. First, modulating effects on olfactory receptor cell differentiation originating from neighboring cells within the olfactory epithelium will be studied. The plan is to examine, in detail, the morphology of disaggregated olfactory epithelial cell cultures, and of reaggregates made from the latter. Preliminary data indicate that differentiation proceeds more expeditiously when reaggregation occurs, thus suggesting that intercellular contact within the epithelium enhances differentiation. It is possible that supporting cells play a role. Monoclonal antibodies to supporting cells will be made in order to provide a means to do immunosurgical experiments in vitro, i.e., to specifically eliminage supporting cells from the cultures by using the antibody (with complement), and thus produce a culture (or reaggregate) containing no supporting cells. Second, the glycoconjugates on axonal surfaces of growing olfactory neurons will be studied with lectin-colloidal gold complexes. Glycoconjugates are important components of cell membranes and presumably play a role in both guidance of olfactory axons as they grow to their synaptic target, and in synaptogenesis. Third, the effect of antidepressant drugs on differentiation will be studied. These studies may lead to a better understanding of the cellular physiology associated with differentiation, specifically the role of calmodulin, cyclic AMP and phosphodiesterase.